Adenocarcinoma of the cervix

Opinion statement Cervical adenocarcinomas are increasing in incidence each year, comprising up to 25% of all cervical cancers diagnosed in the United States. This increase largely reflects the inherent difficulty in detecting glandular precursor lesions using current screening practices. However, there also appears to be a recent shift in the epidemiology of the disease process with younger women being diagnosed more frequently. Fertility-sparing surgery is an option for selected patients with adenocarcinoma in situ or stage IA₁ cervical adenocarcinoma. Simple hysterectomy should be performed at the completion of childbearing or when preserving fertility is not an issue. The treatment of choice for most women with stage IA₂ to IB₁ disease is radical hysterectomy. Fewer than 20% of patients will need adjuvant therapy and the cure rate is excellent. Primary radiation with weekly cisplatin may be the best option for patients with stage IB₂ to IIA cervical adenocarcinoma. Patients treated initially by primary radical surgery will almost certainly require postoperative chemoradiation because of high-risk surgical-pathologic features. Patients with stage IIB to IVA disease should also receive primary radiation with weekly cisplatin. Management of recurrence should be individualized, depending on the location of disease and the type of previous therapy.     

Adenocarcinoma of the uterine cervix

In Finland, the incidence of cervical cancer has shown a decreasing tendency since the 1960s. The same trend, however, has not been noticed in the incidence of cervical adenocarcinoma. The reason for this is not known, although many studies have shown differences in the cause, epidemiology, and biology of the epidermoid and adenocarcinoma of the uterine cervix. A total of 106 new patients with cervical adenocarcinoma were treated at our institution from 1976 to 1980, which represents 20.4% of all cervical carcinomas treated. The mean age of the patients was 58.1 years (range, 29 to 82 years) and the peak incidence was in the group 60 to 69 years of age. Most of the patients were postmenopausal (71.7%) and the main symptom was abnormal vaginal bleeding (78.3%). The proportion of Stage I was 61.3%. Combined operative and radiation therapy was used in 74.5% of the patients. The overall 5-year survival rate was 65.1% (corrected 74.5%), which did not differ from that of patients with squamous cell carcinoma. The most significant prognostic factors were the size of the tumor, presence of pelvic lymph node metastases, and the stage of the disease.     

Adenocarcinoma of the uterine cervix

Between 1958 and 1969, 251 patients were treated at Radiumhemmet in Stockholm for adenocarcinoma of the uterine cervix. The histologic specimens were reevaluated. In the 211 cases of pure adenocarcinoma, the 5-year survival rate was compared with that in the total of cervical epithelial malignancies. The rate was lower in the adenocarcinoma cases, with respective crude 5-year survival rates of 84%, 50%, and 9% in Stages I, II, and III. Two modes of treatment, irradiation alone or irradiation plus radical surgery, were used in Stages IB and IIA. The combined treatment gave significantly improved 5-year survival rates.     

Adenocarcinoma of the uterine cervix

Fifty patients with adenocarcinoma of the uterine cervix were evaluated retrospectively. Treatment was based on the stage and size of tumors and the overall medical condition of the patient. Radical surgery or surgery in combination with radiation therapy was employed whenever possible. The overall survival rate was 50%, with Stage IB survival 74%. Survival in Stage IB patients was adversely affected by increasing tumor grade and size. This closely correlated with a tendency of the tumors to dedifferentiate as they increased in size. Lymph node involvement increased with increasing grade of tumor as well. Survival in patients with advanced disease was dismal. Survival increased with aggressive management which should, if possible, include surgery in Stage I and II disease.     

Adenocarcinoma of the uterine cervix

The prognosis of 589 patients with adenocarcinoma, 387 with mixed type of adenocarcinoma and squamous cell carcinoma of the uterine cervix from 18 hospitals in Japan were evaluated. Stage 0, I a patients with adenocarcinoma or mixed type had good survival. Stage I b, II, III patients had smaller five-year survival (p less than 0.01) than squamous cell carcinoma. Lymph nodes metastasis was related to poorer survival. Radiation therapy or chemotherapy was not sufficient for patients with stage I b, II, III, IV diseases.     

Adenocarcinoma in situ of the cervix

BACKGROUND: The current study examines 1) the sensitivity of detection and 2) sampling and screening/diagnostic error in the cytologic diagnosis of adenocarcinoma in situ (AIS) of the cervix. The data were taken from public and private sector screening laboratories reporting 25,000 and 80,000 smears, respectively, each year. METHODS: The study group was comprised of women with a biopsy diagnosis of AIS or AIS combined with a high-grade squamous intraepithelial lesion (HSIL) who were accessioned by the Western Australian Cervical Cytology Registry (WACCR) between 1993-1998. Cervical smears reported by the Western Australia Centre for Pathology and Medical Research (PathCentre) or Western Diagnostic Pathology (WDP) in the 36 months before the index biopsy was obtained were retrieved. A true measure of the sensitivity of detection could not be determined because to the authors' knowledge the exact prevalence of disease is unknown at present. For the current study, sensitivity was defined as the percentage of smears reported as demonstrating a possible or definite high-grade epithelial abnormality (HGEA), either glandular or squamous. Sampling error was defined as the percentage of smears found to have no HGEA on review. Screening/diagnostic error was defined as the percentage of smears in which HGEA was not diagnosed initially but review demonstrated possible or definite HGEA. Sensitivity also was calculated for a randomly selected control group of biopsy proven cases of Grade 3 cervical intraepithelial neoplasia (CIN 3) accessioned at the WACCR in 1999. RESULTS: For biopsy findings of AIS alone, the diagnostic "sensitivity" of a single smear was 47.6% for the PathCentre and 54.3% for WDP. Nearly all the abnormalities were reported as glandular. The sampling and screening/diagnostic errors were 47.6% and 4.8%, respectively, for the PathCentre and 33.3% and 12.3%, respectively, for WDP. The results from the PathCentre were better for AIS plus HSIL than for AIS alone, but the results from WDP were similar for both groups. For the CIN 3 control cases, the "sensitivity" of a single smear was 42.5%. CONCLUSIONS: To the authors' knowledge epidemiologic studies published to date have not demonstrated a benefit from screening for precursors of cervical adenocarcinoma. However, in the study laboratories as in many others, reasonable expertise in diagnosing AIS has been acquired only within the last 10-15 years, which may be too short a period in which to demonstrate a significant effect. The results of the current study provide some encouraging baseline data regarding the sensitivity of the Papanicolaou smear in detecting AIS. Further improvements in sampling and cytodiagnosis may be possible.     

Adenocarcinoma of the cervix associated with human papillomavirus

Eleven pure adenocarcinomas of the cervix were analyzed for human papillomavirus (HPV) types 6, 11, 16, 18 and 31 by Southern blot hybridizations. Seven tumors were positive for papillomavirus DNA. Five hybridized to the HPV 18 specific probe and two tumors hybridized to HPV 16. All tumors were negative for HPV 6/11 and 31, and no additional tumors became positive with hybridizations under nonstringent conditions to a mixture of HPV probes. No papillomavirus DNA was detected in 11 noncervical malignancies or in six hysterectomy specimens in which cancer was not present. The histopathologic and clinical features of the patients were correlated with the presence of HPV. The women with papillomavirus DNA in their adenocarcinomas tended to be younger (mean age, 37.3) than those that were negative for HPV (mean age, 49.0). The findings suggest that papillomaviruses may be an etiologic factor in the development of some adenocarcinomas of the cervix.     

Adenocarcinoma of the uterine cervix: A study of 37 cases

In a study of 37 patients diagnosed with cervical adenocarcinoma between 1961 and 1994, clinical and pathologic findings were evaluated. Of the 37 patients, 27 (73%) had a pure adenocarcinoma, five (13.5%) had a collision tumor and five (13.5%) had an adenosquamous carcinoma. Twenty-six patients (70.3%) were diagnosed in Stage I, and II (29.7%) patients in Stage II, III, and IV. Two patients (5.4%) were treated with simple hysterectomy alone, nine (24.3%) with simple hysterectomy followed by radiotherapy, eight (21.6%) with radical hysterectomy alone, five (13.5%) with radical hysterectomy followed by radiotherapy, nine (24.3%) with radiotherapy alone, one (2.7%) with radiotherapy followed by simple hysterectomy, and three (8.1%) received no treatment. The actuarial 5-year survival rate was 69%. It is suggested that for patients with small early-stage disease, radical hysterectomy should be primary treatment and postoperative adjuvant radiotherapy would be advocated if high-risk features are histologically demonstrated. For all other patients, radiotherapy should be primary treatment. © 1996 Wiley-Liss, Inc.     

Adenocarcinoma in situ and early invasive adenocarcinoma of the uterine cervix

As data continue to accumulate, the clinical characteristics of preinvasive and early invasive glandular cervical neoplasia are becoming progressively better defined. Cytologic screening for these lesions is imprecise; however, modifications to current classification systems may improve the overall accuracy. All glandular abnormalities on the Papanicolaou smear, nevertheless, require judicious evaluation and careful follow-up. Cervical conization is the most definitive means of diagnosing adenocarcinoma in situ (ACIS). Because ACIS has been thought to represent a multifocal process, with negative conization margins having limited predictive value, conservative management protocols have been difficult to endorse. Several large studies now indicate that the surgical margin status may be a more reliable indicator of true disease clearance than previously thought. For young patients desiring to maintain reproductive capacity, ACIS appears to be safely managed by cold-knife conization combined with diligent surveillance. Early invasive adenocarcinoma of the uterine cervix is associated with an excellent prognosis, and recent data suggest that radical surgery may be unnecessary.     

Adenocarcinoma of the uterine cervix. Prognosis and prognostic significance of histology

Corrected survival rates for 163 cases of adenocarcinoma of the uterine cervix at 5 and 10 years were 51% and 42%, respectively. For clinical Stages I to IV the 5-year survival rates were 71%, 40%, 30%, and 0%, respectively. The frequency of positive lymph nodes was 4% in Stage I and 71% in Stage II adenocarcinomas. For Stage II this figure is much higher than usually reported in squamous cell carcinoma, and suggests that these tumors behave differently. No significant difference in survival rate was found between pure adenocarcinoma, adenosquamous carcinoma, clear cell adenocarcinoma and adenocarcinoma. Histologic grade showed a direct correlation to the survival rate; for grade I tumors it was about 60%, whereas for patients with grade IV tumors only about 10% survived.     

Adenocarcinoma of the uterine cervix: lack of evidence for a poor prognosis

A retrospective analysis was performed to evaluate the prognostic significance of histologic type (epidermoid carcinoma versus adenocarcinoma) on local control of disease and on the development of distant metastatic disease in 1239 patients with carcinoma of the uterine cervix treated with radiation therapy alone or surgery and irradiation at the Radiation Oncology Center, Mallinckrodt Institute of Radiology (MIR), Washington University Medical Center, between 1959 and 1982. The 5-year disease-free survival (all stages combined) was 68.0% for 925 patients with epidermoid carcinoma compared to 64.9% for 79 patients with adenocarcinoma treated with irradiation alone (p = 0.34). There was no significant difference in the survival rate when epidermoid carcinoma and adenocarcinoma were compared after stratification by clinical stage except for stage III. The 5-year disease-free survival (all stages combined) was 73.4% for 213 patients with epidermoid carcinoma and 77.0% for 22 patients with adenocarcinoma treated with irradiation plus surgery (p= 0.74). Prognostic variables analyzed by multivariate analysis included age at diagnosis, histology, size of lesion, endometrial extension, lymph node status (as evaluated by lymphangiogram), dose to point A, and surgery. Prognostic variables that were significant (p less than 0.05) for the development of recurrent disease in the pelvis were size of the primary lesion and dose of irradiation to point A. Significant (p less than 0.05) factors for the development of distant metastatic disease were size of the primary lesion and metastatic lymph nodes at the time of diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adenocarcinoma of the uterine cervix. Prognosis and patterns of failure in 367 cases

Between 1965 and 1985, 367 patients received initial treatment for adenocarcinoma of the uterine cervix at the M. D. Anderson Cancer Center (MDACC). Of the 334 patients treated with curative intent, 223 had International Federation of Gynecology and Obstetrics (FIGO) Stage I, 60 had Stage II, and 51 had Stage III/IV disease. The 5-year and 10-year relapse-free survival (RFS) rates for all patients treated for Stage I disease were 73% and 70%, respectively. RFS was strongly correlated with initial bulk of disease (P = 0.002), although locoregional control (LRC) was good in all groups: 91 patients with a normal-sized cervix (tumor less than 3 cm) had a 5-year RFS rate of 88% and an actuarial LRC rate of 94%; 102 patients with lesions 3 to 5.9 cm in diameter had an RFS rate of 64% and an LRC rate of 82%; and 22 patients with bulky lesions greater than 6 cm in diameter had a comparable LRC rate of 81%, but an RFS rate of only 45%. Decreased RFS also was strongly correlated with positive lymphangiogram (LAG) results (P = 0.02) and poorly differentiated lesions (P = 0.0014). When initial primary tumor size was taken into account, there was no significant difference in RFS or LRC between patients treated with radiation (RT) alone or RT plus extrafascial hysterectomy (R + S). The 5-year and 10-year RFS rates of 60 patients who received curative therapy for Stage II disease were 32% and 25%, respectively, with an LRC rate of 62% at 5 years. Patients with bulky Stage II disease did particularly poorly, with a 5-year RFS rate of 15%. Decreased RFS was correlated with positive LAG results and poorly differentiated tumors. Most Stage II patients whose disease relapsed died with distant metastases (73%). Forty-eight patients with Stage III/IV disease treated with curative intent had a 5-year survival rate of 31% and a 5-year pelvic disease control rate of 52%. In summary, patients with small volume Stage IB lesions have excellent LRC and survival with RT alone. RT achieves good LRC of bulkier Stage I lesions, but survival decreases with increasing primary tumor size. R + S holds no apparent advantage over RT alone. Patients with more advanced disease have a high rate of relapse with frequent distant metastasis. In particular, the survival of patients with FIGO Stage II disease is much lower than what we have observed after treatment of comparable stage squamous carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)     

Adenocarcinoma of the uterine cervix: characteristics of its pathogenesis, clinical picture and diagnosis

The paper discusses the data on 262 cases of cervical carcinoma (adenocarcinoma--138; squamous cell carcinoma--124). The pathogenetic and clinical characteristics, particularly localization, growth and dissemination, of the two malignancies were compared. More than a third of cervical carcinoma patients revealed disturbances in fat and carbohydrate metabolism and ovarian and menstrual function. The endometrium and ovaries were involved in half of them. No such involvement was observed in squamous cell carcinoma patients. Nor any significant disorders occurred in the neuroendocrine system. The hormone dependence of cervical adenocarcinoma and the common nature of its pathogenetic features and those of adenocarcinoma of the endometrium are suggested.     

Adenocarcinoma in situ of the uterine cervix: screening and diagnostic errors in Papanicolaou smears

BACKGROUND: Little attention has been given to the reasons for failure to detect adenocarcinoma in situ (AIS) of the uterine cervix in Papanicolaou (Pap) smears. In the current study, the authors examined a series of screening or diagnostic errors in cases in which the final histologic diagnosis was either AIS or AIS combined with a high-grade squamous intraepithelial lesion (AIS + HSIL). METHODS: Smears obtained in the 3 years before histologically proven AIS or AIS + HSIL was diagnosed and within a specified 6-year period (1993-1998) were reviewed and reclassified. All were conventional Pap smears. The smears studied were those with a review diagnosis of possible or definite high-grade epithelial abnormality that initially were reported by a cytotechnologist to be negative (screening error) or that were reported by a pathologist to be negative, unsatisfactory, or indicative of a low-grade epithelial abnormality (diagnostic error). A semiquantitative, blinded assessment of the frequency of cytologic criteria for the diagnosis of AIS was made for smears with erroneous diagnoses compared with a series of smears that yielded true-positive findings. RESULTS: Sampling errors, which were defined as cases in which smears did not have sufficient evidence for a diagnosis of possible or definite AIS or HSIL on review, accounted for 35.1% and 36% of all smears from patients with a biopsy diagnosis of AIS and patients with a biopsy diagnosis of AIS + HSIL, respectively. With regard to AIS, there were 3 screening errors and 5 diagnostic errors, accounting for 10.4% of 77 smears. Minimal, poorly preserved material was evident in four smears, including three smears with only one sheet of abnormal glandular cells. In four other smears, there was a moderate amount of adequately preserved glandular material, mainly in large sheets, with varying degrees of crowding and hyperchromasia. With regard to AIS + HSIL, there were 6 screening errors and 6 diagnostic errors, accounting for 13.5% of 89 smears. In those smears, there generally was a moderate amount of abnormal material in the form of crowded groups of suboptimally preserved, hyperchromatic squamous cells. Only two of those smears yielded findings of possible abnormal glandular cells. Only 3 of 20 errors occurred in smears that were examined during the last 3 years of the study. In the semiquantitative assessment, smears with erroneous findings were shown to contain far less abnormal material than true-positive smears and to exhibit a corresponding paucity of diagnostic criteria. CONCLUSIONS: Sampling errors were the main cause of false-negative reports in cases of AIS and AIS + HSIL. The primary factors that contributed to screening or diagnostic errors in AIS were minimal, poorly preserved abnormal material and an overly conservative approach to the assessment of unusual large sheets or aggregates of glandular cells. With regard to AIS + HSIL, most laboratory errors were related to the presence of crowded groups of squamous epithelial cells. There were fewer errors in the last 3 years of the study, raising the possibility of improvement over time.     

The histologic diagnosis of adenocarcinoma in situ and related lesions of the cervix uteri. Adenocarcinoma in situ

Seventy-two cases of in situ adenocarcinoma (AIS) of the cervix were reviewed. Forty-five cases had associated cervical intraepithelial neoplasia and 20 cases had changes of wart virus infection. Five cases had associated microinvasive squamous cell carcinoma and one cases showed frankly invasive squamous cell carcinoma (SCC). Of the 72 cases, 41 showed an endocervical type of AIS and three cases an endometrioid type. There was no case of pure intestinal type AIS. Twenty-eight cases showed a mixed pattern. Architectural patterns characterized by tunnel clusters, cribriform glands, glandular budding and papillary formations were assessed. Most cases showed varying combinations of these patterns but in ten cases significant changes were absent. Both cellular apoptosis and mitotic activity were seen in varying degrees in all cases of AIS. The significance of these and other features of AIS are discussed as well as the conditions involved in the differential diagnosis.